2018 Fiscal Year Final Research Report
Translational research to evaluate the resistant mechanism of anti-HER2 antibody by using immunohistochemistry and next-generation sequencing in HER2-positive gastric patients.
| Project/Area Number |
17K15010
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor diagnostics
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| Research Institution | Research Institute for Clinical Oncology, Saitama Cancer Center |
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Principal Investigator |
Takahashi Naoki 埼玉県立がんセンター(臨床腫瘍研究所), 病院 消化器内科, 医長 (20744204)
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| Research Collaborator |
Sawada Takeshi
Sasaki Yasushi
Iwasa Satoru
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | 胃癌 / HER2 / ハーセプチン |
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| Outline of Final Research Achievements |
Trastuzumab is an active HER2 targeted drug and approved for HER2-positive GC patients. The mechanism of the resistance to trastuzumab is unclear and there were few reports to evaluate the RTKs protein expression and genetic alterations by using tumor tissues during the treatment. Our study indicated that HER2 expression disappeared during the treatment of trastuzumab in 42% of HER2-positve GC patients. In addition, the frequency of patinets with high IGF-1R expression statistically increased after treatment. Somatic mutations such as KRAS and BRAF were observed in a part of patients. Although these mutations was reported as the resistance to several molecular target drugs, HER2-positive patients with these mutations achieved response to trastuzumab in our study. HER2 copy number was also evaluated by digital PCR. High copy number of HER2 at pre-treatment was associated with good response of trastuzumab and long duration of the treatment with trastuzumab.
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| Free Research Field |
腫瘍内科
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、転移性胃癌に対するハーセプチン治療中における腫瘍細胞のタンパク発現ならびに遺伝子変化を評価した。これらの腫瘍細胞におけるタンパク発現や遺伝子変化は、分子標的治療薬の治療効果を予測するマーカーとなったり、新たな治療標的として新たな治療開発に繋がる重要な知見となる。HER2発現のみならず、HER2以外のタンパク発現や、癌関連遺伝子も、ハーセプチン治療中に変化が認められている。本研究で得られたたんぱく発現や遺伝子変化のプロファイルは、今後、血液を用いたcfDNAによる網羅的遺伝子解析や新たな治療開発に発展させることが可能であり、学術的ならびに社会的意義は大きいと考える。
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